Predictive Factors of Antiparkinsonian Drug Reduction after Subthalamic Stimulation for Parkinson's Disease.

Subthalamic nucleus deep brain stimulation (STN-DBS) improves motor symptoms in individuals with advanced Parkinson's disease (PD) and enables physicians to reduce doses of antiparkinsonian drugs. We investigated possible predictive factors for the successful reduction of antiparkinsonian drug dosage after STN-DBS. We evaluated 33 PD patients who underwent bilateral STN-DBS. We assessed rates of reduction of the levodopa-equivalent daily dose (LEDD) and levodopa daily dose (LDD) by comparing drug doses before vs. 6-months post-surgery. We used correlation coefficients to measure the strength of the relationships between LEDD and LDD reduction rates and preoperative factors including age, disease duration, preoperative LEDD and LDD, unified Parkinson's Disease Rating Scale part-II and -III, levodopa response rate, Mini-Mental State Examination score, dyskinesia score, Hamilton Rating Scale for depression, and the number of non-motor symptoms. The average LEDD and LDD reduction rates were 61.0% and 70.4%, respectively. Of the variables assessed, only the number of psychiatric/cognitive symptoms was significantly correlated with the LEDD reduction rate. No other preoperative factors were correlated with the LEDD or LDD reduction rate. A wide range of preoperative psychiatric and cognitive symptoms may predict the successful reduction of antiparkinsonian drugs after STN-DBS.

[Peripheral neuropathy as a side effect of chemotherapy and targeted therapy]. / Chemotherapie-induzierte periphere Neuropathie.

Chemotherapy-induced peripheral neuropathy (CIPN) is a severe and common side effect induced by a variety of anticancer drugs. CIPN presents as a sensory, motor, and sometimes autonomic dysfunction with a large variability, from a mild tingling sensation and hyperesthesia, to severe neuropathic pain. Up to 40 % of patients will develop CIPN which may lead to dose-reduction or discontinuation of their current treatment and largely affects their quality of life (QoL). This review presents specific clinical features and pathomechanisms and discusses current preventive strategies and therapeutic options.

Exenatide once weekly versus placebo in Parkinson's disease: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has neuroprotective effects in preclinical models of Parkinson's disease. We investigated whether these effects would be apparent in a clinical trial. METHODS: In this single-centre, randomised, double-blind, placebo-controlled trial, patients with moderate Parkinson's disease were randomly assigned (1:1) to receive subcutaneous injections of exenatide 2 mg or placebo once weekly for 48 weeks in addition to their regular medication, followed by a 12-week washout period. Eligible patients were aged 25-75 years, had idiopathic Parkinson's disease as measured by Queen Square Brain Bank criteria, were on dopaminergic treatment with wearing-off effects, and were at Hoehn and Yahr stage 2·5 or less when on treatment. Randomisation was by web-based randomisation with a two strata block design according to disease severity. Patients and investigators were masked to treatment allocation. The primary outcome was the adjusted difference in the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor subscale (part 3) in the practically defined off-medication state at 60 weeks. All efficacy analyses were based on a modified intention-to-treat principle, which included all patients who completed any post-randomisation follow-up assessments. The study is registered at ClinicalTrials.gov (NCT01971242) and is completed. FINDINGS: Between June 18, 2014, and March 13, 2015, 62 patients were enrolled and randomly assigned, 32 to exenatide and 30 to placebo. Our primary analysis included 31 patients in the exenatide group and 29 patients in the placebo group. At 60 weeks, off-medication scores on part 3 of the MDS-UPDRS had improved by 1·0 points (95% CI -2·6 to 0·7) in the exenatide group and worsened by 2·1 points (-0·6 to 4·8) in the placebo group, an adjusted mean difference of -3·5 points (-6·7 to -0·3; p=0·0318). Injection site reactions and gastrointestinal symptoms were common adverse events in both groups. Six serious adverse events occurred in the exenatide group and two in the placebo group, although none in either group were judged to be related to the study interventions. INTERPRETATION: Exenatide had positive effects on practically defined off-medication motor scores in Parkinson's disease, which were sustained beyond the period of exposure. Whether exenatide affects the underlying disease pathophysiology or simply induces long-lasting symptomatic effects is uncertain. Exenatide represents a major new avenue for investigation in Parkinson's disease, and effects on everyday symptoms should be examined in longer-term trials. FUNDING: Michael J Fox Foundation for Parkinson's Research.

[Reversible posterior leukoencephalopathy syndrome in a patient presenting granulomatosis with polyangiitis]. / Syndrome d'encéphalopathie postérieure réversible au cours d'une granulomatose avec polyangéite.

BACKGROUND: Reversible posterior leukoencephalopathy syndrome (RPLS) is characterised by clinical neurological features of sudden onset and brain MRI findings such as T2/Flair white matter hyperintensities. RPLS can occur in autoimmune diseases, and rarely in systemic vasculitis. We report a case of RPLS in a woman presenting granulomatosis with polyangiitis (Wegener's granulomatosis). PATIENTS AND METHODS: A 22-year-old female patient was treated with methylprednisolone pulses for granulomatosis with polyangiitis and neurological impairment. A few hours after the second pulse, the patient had seizures, blindness and confusion associated with high blood pressure and acute renal failure. MRI revealed a high-intensity area on T2-Flair weighted images of the occipital-temporal lobes. The patient was treated with antiepileptic and antihypertensive medications, oral steroids and cyclophosphamide; the clinical and radiological findings proved reversible over the ensuing days. DISCUSSION: The occurrence of RPLS in systemic vasculitis is rare. Six cases of RPLS associated with granulomatosis and polyangiitis have been reported. It appears important to screen for high blood pressure in patients recently treated with corticosteroids for vasculitis as this condition may represent a precipitating factor for RPLS.

Sex-Specific Alterations of White Matter Developmental Trajectories in Infants With Prenatal Exposure to Methamphetamine and Tobacco.

IMPORTANCE: Methamphetamine is a common illicit drug used worldwide. Methamphetamine and/or tobacco use by pregnant women remains prevalent. However, little is known about the effect of comorbid methamphetamine and tobacco use on human fetal brain development. OBJECTIVE: To investigate whether microstructural brain abnormalities reported in children with prenatal methamphetamine and/or tobacco exposure are present at birth before childhood environmental influences. DESIGN, SETTING, AND PARTICIPANTS: A prospective, longitudinal study was conducted between September 17, 2008, and February 28, 2015, at an ambulatory academic medical center. A total of 752 infant-mother dyads were screened and 139 of 195 qualified neonates were evaluated (36 methamphetamine/tobacco exposed, 32 tobacco exposed, and 71 unexposed controls). They were recruited consecutively from the community. EXPOSURES: Prenatal methamphetamine and/or tobacco exposure. MAIN OUTCOMES AND MEASURES: Quantitative neurologic examination and diffusion tensor imaging performed 1 to 3 times through age 4 months; diffusivities and fractional anisotropy (FA) assessed in 7 white matter tracts and 4 subcortical brain regions using an automated atlas-based method. RESULTS: Of the 139 infants evaluated, 72 were female (51.8%); the mean (SE) postmenstrual age at baseline was 41.5 (0.27) weeks. Methamphetamine/tobacco-exposed infants showed delayed developmental trajectories on active muscle tone (group × age, P < .001) and total neurologic scores (group × age, P = .01) that normalized by ages 3 to 4 months. Only methamphetamine/tobacco-exposed boys had lower FA (group × age, P = .02) and higher diffusivities in superior (SCR) and posterior corona radiatae (PCR) (group × age × sex, P = .002; group × age × sex, P = .01) at baseline that normalized by age 3 months. Only methamphetamine/tobacco- and tobacco-exposed girls showed persistently lower FA in anterior corona radiata (ACR) (group, P = .04; group × age × sex, P = .01). Tobacco-exposed infants showed persistently lower axial diffusion in the thalamus and internal capsule across groups (P = .02). CONCLUSIONS AND RELEVANCE: Prenatal methamphetamine/tobacco exposure may lead to delays in motor development, with less coherent fibers and less myelination in SCR and PCR only in male infants, but these abnormalities may normalize by ages 3 to 4 months after cessation of stimulant exposure. In contrast, persistently less coherent ACR fibers were observed in methamphetamine/tobacco- and tobacco-exposed girls, possibly from increased dendritic branching or spine density due to epigenetic influences. Persistently lower diffusivity in the thalamus and internal capsule of all tobacco-exposed infants suggests aberrant axonal development. Collectively, prenatal methamphetamine and/or tobacco exposure may lead to delayed motor development and white matter maturation in sex- and regional-specific manners.

Potentially Serious Drug-Drug Interactions in Older Patients Hospitalized for Acute Ischemic and Hemorrhagic Stroke.

BACKGROUND: Polypharmacy is very common in older persons and it is associated with inappropriate prescribing and potential drug-drug interactions (DDIs). Aims of this study were to identify prevalence of DDIs in older persons with acute stroke and to evaluate the association between stroke and DDIs. METHODS: One hundred forty-six patients admitted with diagnosis of acute stroke were enrolled. The therapeutic regimen of patients was analyzed at admission to identify the number of DDIs, prevalence and sorts of serious DDIs according to subtype of acute stroke (ischemic or hemorrhagic) and to its recurrence. RESULTS: Five hundred eighty-two DDIs were identified: 18 mild, 415 moderate and 149 serious. Sixty-one percent of patients were exposed to at least one serious DDI. A higher percentage of patients were exposed to at least one serious DDI among those with a recurring ischemic event compared to those with a first event (74 vs. 50%; p < 0.01, respectively). Serious DDIs potentially associated with an increased risk of a cerebral event were identified in 19 (17%) patients with ischemic stroke, and in 7 (19%) patients with hemorrhagic stroke. CONCLUSIONS: The prevalence of serious DDIs was high in aging patients with acute stroke but different according to subtype and recurrence of the cerebrovascular event.

Complications after spinal anesthesia in adult tethered cord syndrome.

Since little has been reported about complications of spinal anesthesia in adult tethered cord syndrome (TCS), we sought to delineate the characteristics of the condition.A total of 4 cases of adult TCS after spinal anesthesia were reviewed. The medical charts of the patients were obtained. Anesthesia, which was combined spinal and epidural anesthesia or spinal anesthesia was performed, and follow-up were carried out in all patients.The most common neurological symptom of adult TCS before surgery was occasional severe pain in back, perineal region, or legs. Frequent micturition, diminished knee and ankle reflexes, and difficulty in bending were exhibited in partial patients. Paraesthesia of perineal region or/and lower extremities existed 2 to 3 days after spinal anesthesia in all the cases. Weakness of lower extremities existed in 1 case. Lumbar magnetic resonance imaging showed the low location of conus medullaris. At follow-up, 3 cases recovered completely within 3 weeks, and 1 case underwent permanent disability.These cases suggest anesthesiologists and surgeons alert to the association of adult TCS and spinal anesthesia. Spinal anesthesia should be prohibited in patients with adult TCS to prevent neurological damages.

Akinetic crisis in dementia with Lewy bodies.

BACKGROUND AND PURPOSE: Dementia with Lewy bodies (DLB) is characterised by neuroleptic hypersensitivity. It is unclear, however, whether the neuroleptic hypersensitivity implies an increased incidence of neuroleptic malignant syndrome (NMS) or of akinetic crisis (AC), which are expressions of the same possibly lethal clinical event, and whether AC in DLB can appear independently of neuroleptic treatment. In our prospective study, we assessed the incidence of AC in a cohort of DLB as compared with that in patients with Parkinson disease (PD). METHODS: In total, 614 patients with PD and 236 DLB were recruited and followed during 2005-2013. AC was diagnosed as sudden akinetic state unresponsive to dopaminergic rescue drugs, dysphagia and serological alterations without recovery for 48 h or more requiring hospital admission. Exposure to neuroleptics was specifically evaluated, because of the high implicit risk in DLB. RESULTS: 24 patients with PD (3.9%) and 16 patients with DLB (6.8%) developed AC. 77 (32.6%) DLB and 32 (5.2%) PD were exposed to typical neuroleptics, but only 8 DLB and 3 PD presented with AC. Disease duration before AC was lower in DLB than in PD group (p<0.01). Outcome was fatal in 8 patients with (50%) DLB and 3 (12.5%) PD (p=0.05). When age and use of neuroleptics were adjusted for into a Cox proportional hazards model predicting time to AC, the HR of patients with DLB was 13.0 (95% CI 4.23 to 39.9; p<0.001). CONCLUSIONS: AC in DLB can appear independently of neuroleptic treatment, occurs earlier and is more frequently fatal than in PD.

Subthalamic nucleus stimulation improves Parkinson's disease-associated camptocormia in parallel to its preoperative levodopa responsiveness.

OBJECTIVE: The aim of this work was to identify factors predictive of postoperative improvement of camptocormia in patients with Parkinson's disease (PD) treated by subthalamic nucleus (STN) stimulation. BACKGROUND: Camptocormia, one of the most disabling features of PD, often responds poorly to medical therapies. The reported effects of deep brain stimulation on PD-associated camptocormia vary, and preoperative characteristics affecting the surgical outcome remain unclear. METHODS: We evaluated 17 patients with camptocormia whose preoperative off-medication thoracolumbar angle exceeded 45°. We used photographs to measure their thoracolumbar angle preoperatively, 3 months after surgery, and at the last follow-up (mean 36.5 months postoperatively) in status on-medication and off-medication. The patient age, duration of PD and camptocormia, daily medications, Unified Parkinson's Disease Rating Scale (UPDRS) subscores and the Schwab-England activity of daily living scale (S-E) were also recorded. Univariate analysis was performed to identify factors predictive of the postoperative improvement of camptocormia. RESULTS: STN stimulation significantly improved the UPDRS subscores and S-E, and resulted in a reduction of daily medications 3 months post-treatment. The preoperative thoracolumbar angle (mean±SD) in status off-medication (84.0±29.5°) was significantly ameliorated 3 months postoperatively (49.8±29.3°) and at the last follow-up (54.8±28.3°). There was no correlation between the postoperative camptocormia improvement rate and preoperative parameters other than the duration and severity of camptocormia and the levodopa responsiveness of the thoracolumbar angle. Symptom duration negatively affected levodopa responsiveness. CONCLUSIONS: STN stimulation improves PD-associated camptocormia in parallel with preoperative levodopa responsiveness. Long symptom duration interferes with levodopa responsiveness.

Hemodynamics during anesthesia for intra-arterial therapy of acute ischemic stroke.

BACKGROUND AND PURPOSE: Many studies have suggested a relationship between the type of anesthesia provided during intra-arterial therapy for acute ischemic stroke and patient outcomes. Variability in blood pressure and hypotension have previously been identified as possible reasons for worse outcomes in acute stroke. Our aim was to investigate hemodynamic parameters and neurological outcomes of patients receiving either general anesthesia or conscious sedation for intra-arterial therapy of acute stroke. METHODS: We performed a retrospective review of patients undergoing intra-arterial therapy from December 2008 to March 2015. Demographic data, baseline National Institutes of Health Stroke Scale score, preoperative physiological variables, procedural details, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate, and modified Rankin Scale scores were recorded. RESULTS: 99 patients were included in the study, with 38 receiving general anesthesia and 61 receiving conscious sedation. Patients who received general anesthesia had a lower maximum SBP (p=0.02), minimum SBP (p<0.0001), minimum DBP (p<0.0001), and minimum MAP (p<0.0001). On multivariate analysis, general anesthesia was associated with lower minimum SBP (p=0.04), DBP (p=0.02), and MAP (p=0.007). Conscious sedation was associated with more favorable neurological outcomes (p=0.02). Patients with favorable neurological outcomes had a lower maximum variability in SBP (p=0.01) and MAP (p=0.03), as well as a higher minimum DBP (p=0.03). CONCLUSIONS: Patients with acute ischemic stroke undergoing intra-arterial therapy with general anesthesia had lower minimum SBP, DBP, and MAP, greater fluctuations in blood pressure, and less favorable outcomes. More studies are needed to examine the implications of variable and reduced blood pressures and neurological outcomes.

Heroin spongiform leukoencephalopathy (HSLE).

PURPOSE: An increasing number of heroin addicts-especially young and first-time users-prefer inhaling the drug to intravenous injection. A rare complication of inhaling heroin is the development of a spongiform leukoencephalopathy (HSLE). METHODS: Pathological background, symptoms, imaging, and therapeutical options are discussed on the basis of an example case. RESULTS: Pathophysiologically, a dysfunction of the oligodendrocyte mitochondria is suspected. Three distinct stages based on key symptoms are defined. Patients may remain in one stage, or pass through two, or all three stages. Magnetic resonance imaging (MRI) is necessary for diagnosis. There are few therapeutical options. Antioxidants and coenzyme Q may be beneficial. The disorder is self-limiting in the majority of cases. Complications such as hydrocephalus and diffuse cerebellar swelling may, however, require neurosurgical intervention. CONCLUSIONS: HSLE is a rare occurrence in patients with heroin abuse. The number of undetected cases in drug-related deaths may be high. Clinical appearance may be easily mistaken for withdrawal symptoms.

Acute pandysautonomia--restitutio ad integrum by high prednisolone therapy.

Acute pandysautonomia is a rare disease defined as acute widespread and severe sympathetic and parasympathetic failure and sparing of somatic nerve fibers. The causes of this syndrome are often an autoimmune disease leading to autonomic ganglionopathy. The majority of cases have a poor prognosis with a chronic debilitating course. We present a previously healthy 24-year-old female patient, who developed a loss of accommodation, pupillotonia, lacrimation, swallowing disturbances, gastrointestinal symptoms and an atonic bladder with 750 ml residual volume. The Ewing battery showed signs of parasympathetic and sympathetic dysfunction leading to the diagnosis of acute pandysautonomia. Further tests failed to find a cause of acute neuropathy especially where there was no evidence for paraneoplastic or infectious etiology. The patient was treated with high dose intravenous prednisolone and completely recovered.

[Pregabalin and gabapentin in multiple sclerosis: clinical experiences and therapeutic implications]. / Ionenkanalmodulatoren bei Multipler Sklerose : Bestandsaufnahme der Anwendung in der Praxis.

BACKGROUND: Due to a plethora of additional symptoms patients with multiple sclerosis (MS) receive symptomatic treatment besides disease-modifying therapies. Among the substances which are commonly used are ion channel modulators (e. g. pregabalin, gabapentin, carbamazepine). The aim of this study was to investigate the use of these drugs in clinical practice in a larger patient cohort. PATIENTS: Data from 533 MS patients [439 without and 94 patients with add-on therapy (treatment group)] were evaluated retrospectively. All patients received a detailed neurological examination including evaluation of EDSS scores. RESULTS: Pregabalin and gabapentin are used most commonly. Abnormal sensations are the most frequent reason for therapy initiation. Patients with higher EDSS values and/or under mitoxantrone treatment most frequently receive additional therapy. CONCLUSION: So far, it is not known whether the investigated agents exert a beneficial influence on the disease course of MS itself beyond a mere symptomatic treatment. Further research efforts and clinical studies are necessary to address this question.

Cerebrovascular events after bevacizumab treatment: an early and severe complication.

BACKGROUND: The indications for bevacizumab (a vascular endothelial growth factor inhibitor) have been expanded recently. Despite concerns for cerebrovascular events from bevacizumab treatment, detailed clinical and radiologic information are lacking. METHODS: Using the Mayo Clinic Rochester database (January 2006-September 2010), we identified bevacizumab-treated patients who developed intracerebral hemorrhage, ischemic stroke or transient ischemic attack within 3 weeks of bevacizumab treatment. Functional recovery was assessed using the modified Rankin scale 3 months following the onset of cerebrovascular events. RESULTS: Ten consecutive patients (median age 58 years, range 37-86) were included in this study. These patients received bevacizumab for a median duration of 3 months (range 2-4 months) for cancer treatment, and developed cerebrovascular events that comprised intratumoral hemorrhage (n = 7), cerebral watershed infarction (n = 1), transient ischemic attack (n = 1), and left vertebral artery occlusion (n = 1). Seven patients had chronic hypertension which was adequately controlled with a single anti-hypertensive agent. Significant increase in blood pressure was observed in nine patients during their acute presentation as compared with their baseline outpatient readings. Six patients died within 3 months of these cerebrovascular events, and the remaining four patients had modest functional recovery. CONCLUSIONS: Cerebrovascular events are early and serious complications that should be considered in bevacizumab-treated patients who present with an acute neurologic deterioration.

Bevacizumab as a treatment option for radiation-induced cerebral necrosis.

Radiation necrosis of normal CNS tissue represents one of the main risk factors of brain irradiation, occurring more frequently and earlier at higher total doses and higher doses per fraction. At present, it is believed that the necrosis results due to increasing capillary permeability caused by cytokine release leading to extracellular edema. This process is sustained by endothelial dysfunction, tissue hypoxia, and subsequent necrosis. Consequently, blocking the vascular endothelial growth factor (VEGF) at an early stage could be an option to reduce the development of radiation necrosis by decreasing the vascular permeability. This might help to reverse the pathological mechanisms, improve the symptoms and prevent further progression. A patient with radiationinduced necrosis was treated with an anti-VEGF antibody (bevacizumab), in whom neurologic signs and symptoms improved in accordance with a decrease in T1-weighted fluid-attenuated inversion recovery signals. Our case report together with the current literature suggests bevacizumab as a treatment option for patients with symptoms and radiological signs of cerebral necrosis induced by radiotherapy.